目的：探讨程序性死亡配体-1（PD-L1）在三阴性乳腺癌（TNBC）组织中的表达及其与脉管生成的相关性。方法：采用组织芯片结合免疫组织化学法检测120 例TNBC组织（收集自河北医科大学第四医院2011 年3 月1 日至2012 年6 月1 日手术切除并经病理证实的TNBC组织标本）中PD-L1 蛋白表达，并分析其与患者各项临床指标关系，同时用CD34 和D2-40 标记血管和淋巴管后检测TNBC中微血管密度（MVD）和淋巴管密度（LVD）。结果：PD-L1 蛋白在TNBC肿瘤细胞及间质浸润淋巴细胞中阳性表达率为56.7%（68/120），PD-L1 的表达与TNBC患者的性别、年龄、临床分期、组织学分级及肿瘤大小均无相关性（P>0.05），但与淋巴结转移情况（P<0.05）及脉管癌栓形成相关（P<0.05）；PD-L1 高表达的TNBC淋巴结转移率高及脉管癌栓形成高，PD-L1的表达与MVD呈正相关关系（r=0.500，P=0.02），PD-L1 的表达与LVD呈正相关（r=0.662，P=0.01）。Log-Rank检验结果显示，PDL1蛋白表达阳性TNBC患者的生存期均显著低于表达阴性的患者（P<0.05)。Cox 多因素分析提示，PD-L1 蛋白表达可作为TNBC整体生存的独立预后因素。结论：PD-L1 在TNBC血管生成及淋巴管生成中起重要作用，其与TNBC的侵袭、转移关系密切，阻断PD1/PD-L1 信号通路有望成为治疗TNBC的有效新策略。

Objective: To investigate the expressions of programmed death ligand 1（PD-L1）in triple-negative breast cancer (TNBC)and its correlation with angiogenesis. Methods: 120 cases of TNBC patients who underwent surgery in the Fourth Hospital of Hebei Medical University from March 1, 2011 to June 1, 2012 were collected. The tumor tissues of patients were surgically resected and confirmed by pathology. PD-L1 protein expression in TNBC tissues of 120 patients was detected by tissue microarray combined with immunohistochemistry,and its relationship with various clinical indicators was analyzed. Blood vessels and lymphatic vessels were labeled withCD34 andD2-40 to detect microvessel density (MVD) and lymphatic vessel density (LVD) in TNBC. Results: The positive expression rate of PD-L1 in the tumor cells and interstitial infiltrating lymphocytes from TNBC was 56.7% (68/120); No correlation was found between PD-L1 protein expression and the gender, age, histological grade, clinical stage, or tumor size of patients with TNBC (P>0.05),but related to the lymph node metastasis (P<0.05) and vascular thrombus (P<0.05). TNBC with high PD-L1 expression exhibited high incidence of lymph node metastasis and formation of vascular thrombus, and the expression of PD-L1 was positively correlated with MVD (r=0.500, P=0.02) as well as LVD (r=0.662, P=0.01). Log-Rank test showed that the survival time of TNBC patients with positive PD-L1 protein expression was significantly shorter than that of patients with negative expression (P<0.05). Cox multivariate analysis suggested that PD-L1 protein expression could be an independent prognostic factor for TNBC overall survival. Conclusion: PD-L1 plays an important role in TNBC angiogenesis and lymphangiogenesis, and is closely related to TNBC invasion and metastasis; blocking PD1/PD-L1 signal pathway is expected to be an effective new strategy for TNBC treatment.

河北省医学科学研究重点课题资助项目（No.20190718）